myeloproliferative disorders

Question 1

What are the 4 main myeloproliferative disorders?

Answer 1

Chronic myelogenous leukemia (CML), Polycythemia vera, Myelofibrosis, Essential thrombocytosis

Question 2

Describe main characteristics of polycythemia vera

Answer 2

Elevated red cell mass and Elevated hemoglobin and hematocrit

Question 3

What are the 3 main causes of polycythemia in general?

Answer 3

Appropriately elevated erythropoietin: hypoxemia. Inappropriately elevated erythropoietin: renal cell carcinoma, hepatocellular carcinoma. Germline and somatic mutation: polycythemia vera

Question 4

What are some epidemiological points of polycythemia vera?

Answer 4

Average age at diagnosis is 60 years of age. Men more common then women.Survival if untreated is 6-18 months. If treated the survival is > 10 years

Question 5

What are symptoms associated with polycythemia vera?

Answer 5

pruritis post bathing, erythromelaglia, HA, weakness, dizziness, excessive sweating

Question 6

What symptoms related to thrombosis are seen with polycythemia vera?

Answer 6

Arterial and venous thrombosis. Amaurosis fugax,
Scintillating scotomata (opthlamic migraine, decreased retinal and choroidal blood flow due to increased blood viscosity)

Question 7

What lab abnormalities are seen with polycythemia vera?

Answer 7

Hgb/HCT > 18.5/56 or > 16.5/50 women. WBC > 10.5. Platlets > 450 K. Elevated serum lactate dehydrogenase. JAK2 mutation in 98%. Abnormal serum erythropoietin. Hypercellular bone marrow. Iron storage in bone marrow is absent

Question 8

What physical findings are expected with polycythemia vera?

Answer 8

Splenomegaly, Facial plethora (ruddy cyanosis), Hepatomegaly, Injection of conjunctival small vessels &/or engorged veins of the optic fundus, Excoriation of the skin, Gouty arthritis and tophi

Question 9

What is treatment for polycythemia vera?

Answer 9

Phlebotomy to keep HCT < 45 men; < 42 women. Low dose aspirin 75-100 mg. Myelosuppressive agents: Hydroxyurea (add if the above treatments are not working or if at high risk for thrombosis with age > 60 or prior thrombotic episode) OR Interferon alpha (use instead of hydroxyurea in women of childbearing age or if hydroxyurea is ineffective)

Question 10

What more serious disorders can polycythemia progress to?

Answer 10

myelofibrosis or acute leukemia

Question 11

What is myelofibrosis?

Answer 11

Replacement of the marrow with collagenous connective tissue fibers

Question 12

What is the epidemiology of myelofibrosis?

Answer 12

Least frequent of the chronic myeloproliferative disorders. Median age 67. Occurs more often in men then women

Question 13

What are major causes of morbidity and mortality associated with myelofibrosis?

Answer 13

Progression to acute leukemia. Infection. Bleeding. Portal hypertension. Vascular complications

Question 14

What clinical manifestations are associated with myelofibrosis?

Answer 14

severe fatigue, LUQ pain(splenomegaly), weight loss, low fever, night sweats, hepatomegaly

Question 15

What symptoms could be secondary to hepatomegaly in myelofibrosis?

Answer 15

Portal hypertension, Ascites, Esophageal and gastric varices, GI bleeding, Hepatic encephalopathy, Portal vein thrombosis

Question 16

What does a blood smear of myelofibrosis show?

Answer 16

Marked poikilocytosis (variation in cell shape) with the presence of tear-drop poikilocytes. There is also anisocytosis.

Question 17

What does a bone marrow biopsy typically show for myelofibrosis?

Answer 17

at early stage: high white count with a left shift, and a hypercellular marrow. at late stage: marrow is replaced with fibrous tissue

Question 18

What are treatment options for myelofibrosis?

Answer 18

Stem cell transplant. Hydroxyurea. chemotherapeutic agents. JAK2 inhibitors: ruxolitinib (Jakafi) $9K/month. Splenectomy but may cause worsening hepatomegaly and decline in liver function. Radiation therapy

Question 19

What is essential thrombocytosis?

Answer 19

Uncommon myeloproliferative condition in which there is isolated thrombocytosis. Abnormal platelet function that can lead to thrombosis and bleeding. Occurs age > 50, more common in women

Question 20

What are lab results associated with essential thrombocytosis?

Answer 20

Platelet counts can be markedly elevated. White blood counts may be slightly elevated. normal RBC morphology. Bone marrow biopsy reveals increased numbers of megakaryocytes. High frequency of JAK2 mutations

Question 21

What are symptoms secondary to elevated platelet count in essential thrombocytosis?

Answer 21

HA, Lightheadedness, Visual changes, Numbness, tingling or burning in the feet (erythromelalgia, Splenomegaly, History of thrombosis

Question 22

Where is thrombosis likely to occur?

Answer 22

Arterial thrombosis is most likely to occur in the hands, feet and brain. Venous thrombosis of mesenteric, hepatic and portal vein, and deep vein thrombosis

Question 23

What are treatment options for essential thrombocytosis?

Answer 23

Low dose aspirin (81 mg/day) and Hydroxyurea to keep platelet count below 500,000

Question 24

What can result as potential progression of essential thrombocytosis?

Answer 24

Bone marrow may become fibrotic. Massive splenomegaly may occur. progression to myelofibrosis after 15 years. progression to acute myelogenous leukemia over 20 years